Abstract
The identification of novel, molecularly defined neoplasms continue to refine diagnostic precision and illuminate tumor pathogenesis. Assessment of the EWSR1 locus has emerged as a frequently utilized diagnostic tool in the work-up of salivary and craniofacial bone tumors, due to its established perturbations in hyalinizing clear cell carcinomas, myoepithelial carcinomas, rare mucoepidermoid carcinomas, and others. Here, we report a case of a 12-year-old female who presented with a large expansile intraosseous lesion within the left body of the mandible, initially biopsied with negative FISH results for EWSR1, but RNA-sequencing identified an EWSR1::YY1 rearrangement. The subsequent resection is presented here and shows an epithelial immunophenotype tumor without myoepithelial differentiation. To the best of our knowledge, this represents a novel epithelial tumor harboring an EWSR1::YY1 fusion outside the peritoneal/visceral cavity. The EWSR1::YY1 fusion is a recently described genetic event, initially reported in epithelioid peritoneal mesothelioma, and represents the first direct oncogenic involvement of the transcription factor YY1.